Patients With Advanced NSCLC Face Critical Treatment Gaps

Effective treatment options for patients battling advanced or metastatic non–small cell lung cancer (NSCLC) remain critically limited, highlighting a significant unmet medical need.¹ A new retrospective cohort study published in JAMA Network Open, drawing on a vast US nationwide electronic health record database from 2018 to 2023, sheds light on the real-world clinical treatment patterns and patient outcomes following platinum-based chemotherapy and anti–PD-1 or anti–PD-L1 regimens.

Approximately 80% to 85% of lung cancer diagnoses in the US are NSCLC.² These findings underscore the urgent necessity for novel therapeutic strategies, particularly innovative immuno-oncology combinations.¹

Novel therapeutic strategies for NSCLC are needed, particularly innovative immuno-oncology combinations.

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The study aimed to describe the clinical journey of patients with advanced or metastatic NSCLC in second- and third-line treatment settings. Researchers focused on key outcomes, including time to treatment discontinuation, progression-free survival, and overall survival in patients who had previously received platinum-based chemotherapy and anti–PD-(L)1 therapy, either combined in 1 line or sequentially in 2 lines, and subsequently initiated at least 1 further treatment. Patients 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 were included, with a median follow-up duration of 7.8 months.

The comprehensive analysis encompassed 1793 patients, with slightly more men (54.3%) than women. The mean age at the start of the index treatment was 67.4 years. The cohort was diverse, with 66.5% identifying as White, 12.2% as Black or African American, and 1.6% as Asian. A vast majority (90.7%) presented with stage IV disease, and common metastatic sites included bone (24.0%) and brain (9.9%). Most patients (84.9%) received treatment exclusively in community settings.

Patients had received their initial platinum-based chemotherapy and anti–PD-(L)1 therapy in various patterns: 73.5% received them as a single combination line, while 22.5% received first-line platinum-based chemotherapy followed by second-line anti–PD-(L)1, and 4.1% received first-line anti–PD-(L)1 followed by second-line platinum-based chemotherapy.

Next-Line Therapy Lacks Standardization

Following these initial regimens, patients received a broad spectrum of subsequent "index treatments," highlighting the lack of a standardized, highly effective next-line therapy. The most frequently observed index treatments included docetaxel plus ramucirumab (17.5%), docetaxel monotherapy (8.8%), and carboplatin plus paclitaxel (7.6%). However, these 3 treatments collectively accounted for only about one-third of the patients, indicating significant variability in clinical practice. After the index treatment, 38.5% of patients went on to receive yet another line of therapy, with gemcitabine, docetaxel plus ramucirumab, and pembrolizumab being the most common post-index treatments.

Overall, the median time from index treatment to treatment discontinuation was just 3.71 months. Median progression-free survival was 5.29 months, and median overall survival was 11.20 months. These outcomes were numerically shorter in patients who received chemotherapy monotherapy as their index treatment, a category that included frequently used therapies like docetaxel and gemcitabine monotherapies.

"This unmet need was particularly evident among patients who subsequently received chemotherapy monotherapy, such as docetaxel," The authors wrote. "Exploratory analyses suggest that treatment with immuno-oncology regimens may be associated with improved outcomes given the favorable outcomes observed in patients receiving immuno-oncology monotherapy or combination regimens following platinum-based chemotherapy and anti–PD-(L)1 regimens. The patterns observed here should motivate further research into novel modalities that extend survival, including immuno-oncology combinations, in this patient population and provide insights relevant to clinical trial design (eg, relevant comparator arms) and evaluation of emerging agents."

References

1. Velcheti V, Moore J, Solem CT. Treatments and outcomes after platinum-based chemotherapy and anti–PD-(L)1 in NSCLC. JAMA Netw Open. 2025;8(6):e2514527. doi:10.1001/jamanetworkopen.2025.14527

2. American Cancer Society. What is lung cancer? Accessed July 10, 2025. http://www.cancer.org/cancer/types/lung-cancer/about/what-is.html